Interleukin-1alpha inhibits insulin signaling with phosphorylating insulin receptor substrate-1 on serine residues in 3T3-L1 adipocytes.
Interleukin-1alpha inhibits insulin signaling with phosphorylating insulin receptor substrate-1 on serine residues in 3T3-L1 adipocytes.
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发表时间：
2006
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通讯作者：
Jianying He;I. Usui;K. Ishizuka;Yukiko Kanatani;K. Hiratani;M. Iwata;A. Bukhari;T. Haruta;T. Sasaoka;Masashi Kobayashi
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作者：
Jianying He;I. Usui;K. Ishizuka;Yukiko Kanatani;K. Hiratani;M. Iwata;A. Bukhari;T. Haruta;T. Sasaoka;Masashi Kobayashi
促炎细胞因子最近被报道抑制胰岛素信号导致胰岛素抵抗。il -1也是促炎细胞因子之一；然而，il -1 α是否也可能引起胰岛素抵抗尚不清楚。在这里，我们研究了il -1 α处理对3T3-L1脂肪细胞胰岛素信号传导的影响。il -1 α处理长达4小时没有改变胰岛素刺激的胰岛素受体酪氨酸磷酸化，而胰岛素受体底物(IRS)-1的酪氨酸磷酸化和与磷脂酰肌醇3-激酶的关联被部分抑制，最大抑制在15分钟左右。il -1刺激后约15分钟，IRS-1在一些丝氨酸残基上短暂磷酸化，当时几个丝氨酸激酶，IkappaB激酶，c- jun - n末端激酶，ERK和p70S6K被激活。这些激酶的化学抑制剂抑制il -1诱导的IRS-1丝氨酸磷酸化。IRS-1的酪氨酸磷酸化仅被IKK抑制剂或JNK抑制剂恢复，提示这两种激酶特异性参与。胰岛素刺激的Akt磷酸化和2-脱氧葡萄糖摄取不受il -1 α的抑制。有趣的是，在IL-6存在的情况下，Akt的磷酸化被il -1 - α协同抑制。综上所述，短期il -1 - α治疗通过丝氨酸磷酸化在IRS-1水平瞬时引起胰岛素抵抗。在其他细胞因子如IL-6存在的情况下，il -1 α可能抑制IRS-1下游的胰岛素信号。
Proinflammatory cytokines are recently reported to inhibit insulin signaling causing insulin resistance. IL-1alpha is also one of the proinflammatory cytokines; however, it has not been clarified whether IL-1alpha may also cause insulin resistance. Here, we investigated the effects of IL-1alpha treatment on insulin signaling in 3T3-L1 adipocytes. IL-1alpha treatment up to 4 h did not alter insulin-stimulated insulin receptor tyrosine phosphorylation, whereas tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the association with phosphatidylinositol 3-kinase were partially inhibited with the maximal inhibition in around 15 min. IRS-1 was transiently phosphorylated on some serine residues around 15 min after IL-1alpha stimulation, when several serine kinases, IkappaB kinase, c-Jun-N-terminal kinase, ERK, and p70S6K were activated. Chemical inhibitors for these kinases inhibited IL-1alpha-induced serine phosphorylation of IRS-1. Tyrosine phosphorylation of IRS-1 was recovered only by the IKK inhibitor or JNK inhibitor, suggesting specific involvement of these two kinases. Insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake were not inhibited only by IL-1alpha. Interestingly, Akt phosphorylation was synergistically inhibited by IL-1alpha in the presence of IL-6. Taken together, short-term IL-1alpha treatment transiently causes insulin resistance at IRS-1 level with its serine phosphorylation. IL-1alpha may suppress insulin signaling downstream of IRS-1 in the presence of other cytokines, such as IL-6.